2. Academic Validation
  3. Identification of a novel RAMP-independent CGRP receptor antagonist

Identification of a novel RAMP-independent CGRP receptor antagonist

  • Bioorg Med Chem Lett. 2011 Nov 15;21(22):6705-8. doi: 10.1016/j.bmcl.2011.09.056.
C Blair Zartman 1,  Ian M Bell,  Steven N Gallicchio,  Samuel L Graham,  Stefanie A Kane,  John J Mallee,  Ruth Z Rutledge,  Christopher A Salvatore,  Joseph P Vacca,  Theresa M Williams
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. blair_zartman@merck.com
PMID: 21982500 DOI: 10.1016/j.bmcl.2011.09.056
Abstract

Identification of an HIV Integrase Inhibitor with micromolar affinity for the CGRP Receptor led to the discovery of a series of structurally novel CGRP Receptor antagonists. Optimization of this series produced compound 16, a low-molecular weight CGRP Receptor Antagonist with good pharmacokinetic properties in both rat and dog. In contrast to Other nonpeptide antagonists, the activity of 16 was affected by the presence of divalent cations and showed evidence of an alternative, RAMP-independent CGRP Receptor binding site.

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